PROJECT SUMMARY The consequences of asymmetric peripheral dysfunction are especially profound in the auditory system, where cochlear receptor cells are not spatially organized. Thus, auditory spatial information is available exclusively through central processing of binaural signals. Asymmetric hearing loss (AHL), which is one of the most common forms of hearing impairment, profoundly disrupts spatial hearing and related functions such as differentiating spatially-separated signals in noise (SIN). Remarkably, disabilities across hearing domains are generally more severe in AHL patients than in equivalent cases of symmetric hearing loss (SHL), and more severe than predicted by peripheral dysfunction. These disabilities are further compounded by problematic downstream outcomes including tinnitus, cognitive impairment, and reduced quality of life. Increasing recognition of the severe disabilities associated AHL has generated interest in a thorough understanding of its central consequences, especially reorganization at the level of primary auditory cortex (ACtx). Binaural cortical plasticity is traditionally assessed by shifts in characteristic frequency (CF) estimates obtained from the hemisphere contralateral to the impaired ear. In general, CFs obtained from the impaired ear shift toward frequencies of surviving cochlear cells. Although previous research has focused on shifts in spectral processing, evaluation of changes in alternative response characteristics are needed to understand the neural basis of the profound deficits in processing speech and SIN observed in AHL patients. Moreover, although difficulties understanding SIN, such as speech in noisy environments, constitutes the largest clinical challenge in AHL, no previous studies have directly investigated SIN processing in the central auditory pathway, or in controlled animal behavioral experiments. The knowledge obtained in such preparations could generate novel insights into the mechanisms underlying this debilitating condition and greatly facilitate the development of new clinical interventions. With these goals in mind, we propose to conduct a multifaceted analysis of altered SIN processing and cortical receptive field alteration following AHL using a transgenic mouse model. We will augment classic pure-tone response metrics such as CF and threshold with spectrotemporal receptive field (STRF) parameters including excitation-inhibition (E-I) ratio and temporal processing capabilities, which are critical for perception of speech and SIN. We will further provide a detailed description of disrupted cortical SIN processing in AHL by presenting elements of vocal communication signals in a range of competing background noise levels. We will compare these outcomes to behavioral deficits in SIN processing in mice performing an auditory discrimination task. The wealth of new insights made possible by this approach are capable of resolving numerous outstanding questions regarding central reorganization in AHL. As a result, clinical researchers will be equipped with new and better-defined central biomarkers of AHL, facilitating the development of improved rehabilitation strategies.